Open AccessMusculoskeletal Differentiation of Cells Derived from Human Embryonic Germ Cells
Author(s) -
Kim Myoung Sook,
Hwang Nathaniel S.,
Lee Janice,
Kim TaeKyun,
Leong Kam,
Shamblott Michael J.,
Gearhart John,
Elisseeff Jennifer
Publication year - 2005
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2004-0110
Subject(s) - biology , microbiology and biotechnology , embryonic stem cell , chondrogenesis , stem cell , aggrecan , cartilage , mesenchyme , embryoid body , immunology , adult stem cell , anatomy , pathology , mesenchymal stem cell , genetics , medicine , articular cartilage , alternative medicine , gene , osteoarthritis
Stem cells have the potential to significantly improve cell and tissue regeneration therapies, but little is understood about how to control their behavior. We investigated the potential differentiation capability of cells derived from human embryonic germ (EG) cells into musculoskeletal lineages by providing a three‐dimensional environment with increased cell–cell contact and growth factors. Cells were clustered into pellets to mimic the mesenchyme condensation process during limb development. LVEC cells, an embryoid body–derived (EBD) cell culture generated from EG cells, were cultured in micromass pellets for 21 days in the presence of bone morphogenetic protein 2 (BMP2) and/or transforming growth factor beta‐3 (TGFβ3). Gene expression for cartilage‐, bone‐, and muscle‐specific matrix proteins—including collagen types I, II, III, IX, X; aggrecan; cartilage proteoglycan link protein; cartilage oligomeric protein; chondroitin sulfate‐4‐S; and myf5—was upregulated in the pellets treated with TGFβ3, while mRNAs for neurofilament heavy (NFH), a neuron marker, and flk‐1, a hematopoietic marker, decreased. Total collagen and proteoglycan production exhibited a time‐dependent increase in the pellets treated with TGFβ3, further confirming the expression of characteristic musculoskeletal markers. Furthermore, our results indicate the ability to select or differentiate stem cells toward a musculoskeletal lineage from a heterogenous EBD cell line.